The role of oncogenes that code for DNA binding proteins, transcriptional factors and cellular proteins that mediate signal transduction in the regulation of viral gene expression, we analyzed the expression of c-fos c- myc and v-src (a tyrosine kinase expressed in T cells) in human PBLs and H9 and U937 cells following infection with HIV-1. Quiescent PBLs were infected with serum-free medium in the presence or absence of IL-2. At various times after infection DNA and RNA were analyzed for the presence of viral and oncogene sequences and cells fixed for analysis of antigen by flow-cytometry. A 20 fold increase in c-fos RNA and a 4-5 fold increase in antigen was observed between 2 and 22 hours post infection. This increase was inhibited by Actinomycin D. No significant change was observed in c- myc expression. HIV-1 sequences were first detected in genomic DNA at 2 hours and viral transcripts between 2 and 4 hours post-infection. In similar experiments performed on H9 and U937 cells a 5-fold increase in v- src antigen levels was observed. This increase was inhibited by AZT. Our preliminary results suggest that enhancement of some of these genes, viz c- fos, v-src may plan a role in regulating viral replication in infected cells. Similar studies are in progress with HUT-78 and CEM cells infected with HIV-2. The role of kinases such as fyn, lck, raf/mil and other oncogenes expressed in hematopoietic cells, viz. ets, rel and fgr and cytokines IL-4, IL-6 and TNFa in HIV-1 and HIV-2 infected cells and their regulation by anti-HIV agents which would enable us to further define the stages of viral replication at which these gene products may function.